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Flavonoids are a group of bioactive compounds that are extensively found in foodstuffs of plant origin. Their regular consumption is associated with reduced risk of a number of chronic diseases, including cancer, cardiovascular disease (CVD) and neurodegenerative disorders. Flavonoids are classified into subgroups based on their chemical structure: flavanones, flavones, flavonols, flavan-3-ols, anthocyanins and isoflavones. Their actions at the molecular level include antioxidant effects, as well the ability to modulate several key enzymatic pathways. The growing body of scientific evidence indicates that flavonoids play a beneficial role in disease prevention, however further clinical and epidemiological trials are greatly needed. Among dietary sources of flavonoids there are fruits, vegetables, nuts, seeds and spices. Consumption of these substances with diet appears to be safe. It seems that a diet rich in flavonoids is beneficial and its promotion is thus justifiable.
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Rocz Panstw Zakl Hig 2014;65(2):79-85
*Corresponding author: Dorota Szostak-Węgierek, Zakład Żywienia Człowieka, Warszawski Uniwersytet Medyczny,
ul. Ciołka 27, 01-445 Warszawa, tel. +48 22 8360913,
© Copyright 2013 by the National Institute of Public Health - National Institute of Hygiene
Aleksandra Kozłowska1, Dorota Szostak-Węgierek2*
1 Department of Preventive Medicine and Hygiene, Institute of Social Medicine, Medical University of Warsaw, Poland
2 Department of Human Nutrition, Faculty of Health Science, Medical University of Warsaw, Poland
Flavonoids are a group of bioactive compounds that are extensively found in foodstuffs of plant origin. Their regular con-
sumption is associated with reduced risk of a number of chronic diseases, including cancer, cardiovascular disease (CVD)
and neurodegenerative disorders. Flavonoids are classified into subgroups based on their chemical structure: flavanones,
flavones, flavonols, flavan-3-ols, anthocyanins and isoflavones. Their actions at the molecular level include antioxidant
effects, as well the ability to modulate several key enzymatic pathways. The growing body of scientific evidence indicates
that flavonoids play a beneficial role in disease prevention, however further clinical and epidemiological trials are greatly
needed. Among dietary sources of flavonoids there are fruits, vegetables, nuts, seeds and spices. Consumption of these sub-
stances with diet appears to be safe. It seems that a diet rich in flavonoids is beneficial and its promotion is thus justifiable.
Key words: flavonoids, cancer, cardiovascular diseases, neurodegenerative disorders
Flawonoidy to grupa związków bioaktywnych występujących powszechnie w żywności pochodzenia roślinnego. Aktualne
dane literaturowe wskazują, że substancje te, spożywane wraz z dietą człowieka, wykazują działanie ochronne przed wie-
loma chorobami przewlekłymi, w tym przed niektórymi nowotworami oraz schorzeniami układu sercowo-naczyniowego,
a ponadto pozytywnie wpływają na układ nerwowy. W zależności od struktury chemicznej wyróżnia się takie podklasy
flawonoidów jak: flawony, flawanony, flawonole, flawanole, antocyjany i izoflawony. Przypuszcza się, że mechanizm
działania tych substancji opiera się na ich silnych właściwościach antyoksydacyjnych oraz innych mechanizmach, takich
jak zdolność do modulowania licznych szlaków enzymatycznych. W wielu badaniach wykazano ich korzystne działanie w
prewencji chorób przewlekłych. Jednakże poznanie dokładnego metabolizmu tych substancji wymaga prowadzenia dalszych
badań. Źródłami flawonoidów w diecie człowieka są warzywa, owoce, orzechy i nasiona, a także niektóre przyprawy. Spo-
żywanie tych substancji wraz z dietą człowieka wydaje się być bezpieczne. Uzasadnionym zatem wydaje się promowanie
diety bogatej we flawonoidy.
Słowa kluczowe: flawonoidy, nowotwory, choroby sercowo-naczyniowe, choroby neurodegeneracyjne
Flavonoids are a diverse group of plant metabolites
with over 10,000 compounds that have been identified
until now. However, only very few of them have been
investigated in detail [25]. They have several important
functions in plants, such as providing protection against
harmful UV radiation or plant pigmentation. In addition,
they have antioxidant, antiviral and antibacterial proper-
ties. They also regulate gene expression and modulate
enzymatic action [25]. All naturally occurring flavono-
ids possess three hydroxyl groups, two of which are on
the ring A at positions five and seven, and one is located
on the ring B, position three. Biochemical actions of
flavonoids depend on the presence and position of va-
rious substituent groups, that affect metabolism of each
compound. They can be found in free or bound forms:
aglycones or β-glycosides [17]. The flavonoid subc-
lasses, based on types of chemical structure, include:
flavonols, flavones, flavanones, flavanols, anthocyanins
and isoflavones [17, 20]. Table 1 shows some common
examples according to this classification.
Antioxidant properties of foodstuffs depend not only
on polyphenol content, but also on their type. For in-
stance, quercetin and catechin demonstrate the greatest
antioxidant properties in vitro [6, 11, 36]. However, their
A. Kozłowska, D. Szostak-Węgierek
80 Nr 2
human metabolism is incompletely understood. Current
studies on biological effects of flavonoids focuse on
their absorption mechanisms, metabolism and bioava-
ilability. Thus, in order to elucidate their physiological
role, molecular studies are required. The results would
enable to evaluate their effectiveness in the treatment
and prevention of certain diseases, together with even-
tual risks arising from their use [18, 33].
At present, consumption of dietary flavonoids is
regarded as safe. Nevertheless, it is worth noting that the
use of pharmaceutical products that contain high doses
of bioactive substances is increasing. Such supplements
provide an alternative source of flavonoids to those ob-
tained from the diet. It is of concern that the toxicity of
concentrated sources of flavonoids is unknown, together
with their interactions with other dietary components or
taken medications [12]. Administration of large doses of
a single flavonoid may decrease bioavailability of trace
elements, vitamins or folic acid. Besides, it may exert
an adverse effect on the thyroid function [12]. There is
a special concern about possible side effects of taking
several flavonoid-containing products at the same time
as flavonoid-flavonoid interactions are little known so
far [12]. A consumer may be misled that flavonoids are
entirely safe because they are so-called ’natural’ pro-
ducts. Uncontrolled use of pharmaceutical preparations
containing flavonoids may come out disadvantageous
for health. Furthermore, the packaging labels for some
dietary supplements have scant information about sa-
fety, adverse reactions, interactions, contraindications,
and efficacy [7, 12].
It is clear that the molecular mechanisms of action
of flavonoids need to be thoroughly understood and
intensive research on this problem should be performed.
However, it should be emphasised that in the light of
recent findings the best and safest source of these sub-
stances is a properly balanced diet.
It is estimated that inhabitants of the Western Europe
consume on average 100 – 1000 mg flavonoids/day/
person [17, 36]. This was confirmed by the European
Prospective Investigation into Cancer and Nutrition
(EPIC) study, which showed the median daily intake
of flavonoids in Greek and Spaniard subjects equal
to 93 mg (n ≥ 28,000) and 126.1 mg (n = 40,683) per
Table 1. Subclasses of flavonoids; authors’ selection based
on [17]
Subclass Examples of compounds
Flavonols Quercetin, kaempferol, myricetin
Flavones Luteolin, apigenin, tangeretin
Flavanones Naringenin, hesperetin
Flavanols, Catechin, epicatechin, epigallocatechin,
glausan-3-epicatechin, proanthocyanidins
Anthocyanins Cyanidin, delphinidin, pelargonidin, malvidin
Isoavones Genistein, daidzein
Table 2. Content of flavonoids, according to their sub-
-classes, in chosen foodstuffs (mg/100g foodstuff);
authors’ selection based on [2]
Flavanones Flavones
Artichokes 12.51 Kohlrabi 1.3
Grapefruit juice 18.98 Red grapes 1.3
Orange juice 18.99 Lemons 1.9
Oranges 42.57 Chicory 2.85
Limes 46.40 Celeriac 3.90
Lemons 49.81 Green pepper 4.71
Grapefruit 54.50 Artichokes 9.69
Dried oregano 412.13 Fresh parsley 216.15
Dried oregano 1046.46
Dried parsley 4523.25
Flavonols Anthocyanins
Apples Mean
3.40 Hazel nuts 6.71
Cooked brussel sprouts 5.24 Morello cherries 7.45
Fresh gs 5.47 Pears 12.18
Dried & sweetened
cranberries 6.91 Black grapes 21.63
Buckwheat 7.09 Red table wine 23.18
Chicory 8.94 Pecan nuts 25.02
Morello cherries 9.41 Strawberries 27.76
American bilberries 10.59 Red bilberries 40.15
Blackcurrants 11.53 Raspberries 40.63
Cooked asparagus 15.16 Red cabbage 63.50
Fresh cranberries 21.59 Red currants 75.02
Goji berries 31.20 Blackberries 90.64
Red onions 38.34 American
bilberries 141.03
Rocket lettuce 69.27 Black currants 154.77
Radish 78.09 Chickpeas 262.49
Sorrel 102.20 Bilberries 285.21
Elderberry juice
concentrate 108.16 Aronia 349.79
Dried parsley 331.24 Elderberry juice
concentrate 411.4
Fresh capers 493.03
Apple juice 5.96 Cooked broad
beans 20.63
Apricots 8.41 Blackberries 42.5
Peaches 8.6 Cocoa, dry powder 52.73
Apples 9.17 Dark chocolate 108.60
Red table wine 11.05 Black tea, brewed 115.57
Pecan nuts 15.99 Green tea, brewed 116.15
Flavonoids – food sources and health benefits 81Nr 2
person respectively [9, 39]. The Greek survey was
performed in 1992 – 1996 and thus the results may be
underestimated as the database concerning flavonoid
levels in foodstuffs was incomplete that time. On the
other hand, it is assumed that inhabitants of countries
in the Far East, such as Japan, because of high intake
of legumes, soy and tea, may consume up to 2 g of
flavonoids daily [36]. In contrast, the Polish National
Multi-centre Health Survey (WOBASZ) demonstrated
that the mean flavonoid intake in the Polish population
was 1 g/person/day [41].
Important dietary sources of flavonoids are vege-
tables, fruits, seeds, some cereals, together with wine,
tea and certain spices. Table 2 demonstrates flavonoid
content in chosen foodstuffs. It should be noted that
the presence of particular flavonoids in vegetables and
fruits depends on the crop variety, location and type of
cultivation, as well as the specific plant morphological
part [13]. Differences in flavonoid contents between
varieties of species are usually small, although in a
few cases very high amounts have been observed, e.g.
in certain berries and tea prepared from leaves of the
Quingmao tree [2].
The well recognised anti-oxidant properties of
flavonoids resulted in the interest about their potential
role in prevention of cardiovascular diseases [18]. For
example, a recent study clearly showed health benefits
of dietary flavonoids as there was a positive association
between their intake and reduction of the risk of car-
diovascular death in adult Americans [22]. The study
demonstrated that both male and female subjects who
consume large amounts of flavonoids (the top quintile)
had the 18% lower mortality risk of cardiovascular di-
seases (CVD) compared to those whose intake was in
the lowest quintile. Another study [3] demonstrated that
high flavonoid consumption (flavones and flavanols)
protected against hypertension. Subjects whose intake of
these substances was in the top quintile, in comparison
with those of the lowest consumption, exhibited the
8% risk reduction of development of this condition [3].
Atherosclerosis is a multifactorial disease. High
blood concentration of oxidatively modified low den-
sity lipoproteins (ox-LDL) accelerates its development.
Other causative factors include blood vessel inflamma-
tion and disorders of coagulation [18, 31]. Because of
their antioxidant and chelating properties, flavonoids
inactivate reactive oxygen species (ROS) and this
way counteract plasma LDL oxidation and ameliorate
inflammation of the blood vessel endothelium. Further-
more, flavonoids decrease activity of xanthine oxidase,
NADPH oxidase, and lipoxygenase ie. the enzymes that
increase ROS production. Anti-arteriosclerotic action of
flavonoids is related also to the reduction of inflamma-
tion in the blood vessel wall through inhibition of the
influx of leucocytes. Flavonoids also decrease activity
of such enzymes as 15-lipoxygenase (15-LOX) and
cyclooxygenase (COX, particularly COX-2). These
enzymes participate in formation of, prostaglandins
and leukotrienes, substances that mediate inflamma-
tion, from arachidonic acid. Decline in their secretion
results in reduction of synthesis of prostaglandin PGE2,
leukotriene B4 and thromboxane A2, what in turn leads
to decrease in inflammation and platelet aggregation.
Inhibition of these enzymes results also in protection of
LDL against oxidation and regulates capillary pressure
back to normal [18].
Beyond of protection of blood vessels against ox-
-LDL, antiatheromatous action of flavonoids results also
from suppression of 3-hydroxy-3-methylglutaryl-coen-
zyme A reductase (HMG-CoA) activity. This enzyme
plays a key role in the synthesis of cholesterol in the
human body, and thereby influences its plasma levels.
Inhibition of its activity lowers intracellular cholesterol
concentrations and results in the following increase in
expression of LDL receptors. This in turn raises the
cellular lipoprotein uptake and removal of cholesterol
from the circulation. Hesperetin is a good example of a
flavonoid, found in lemons and oranges, which reduces
blood cholesterol level in the aforementioned way [18].
Furthermore, a randomised, double-blind study, that
included cell culture, demonstrated in subjects with
metabolic syndrome that oral administration of 500 mg
of hesperetin daily over 3 weeks stimulated endothelial
nitric oxide (NO) formation, what was probably related
to the decreased activity of proinflammatory cytokines.
This study showed that a three week hesperetin sup-
plementation improves endothelial function, reduces
inflammation and beneficially affects lipid profile in
patients with metabolic syndrome [27].
It was shown that such flavonoids as rutin and its
derivatives, along with hesperetin, help seal and rein-
force blood vessel walls [18, 23]. These substances,
similarly to vitamin C, enhance collagen synthesis and
thus make the connective tissue in blood vessels more
elastic. Rutin and its derivatives are used as a medica-
tion aimed at regulation of capillary permeability and
improvement of peripheral circulation [23]. Flavonoids,
such as quercetin or rutin, have anti-aggregating pro-
perties, and thereby reduce the risk of clot formation
near the damaged endothelium [18]. By interaction with
platelet integrins, these substances prevent platelets
from sticking. They also stimulate NO formation in the
vascular endothelium what facilitates vasodilation, and
thus plays a key role in regulation of blood pressure [18].
A. Kozłowska, D. Szostak-Węgierek
82 Nr 2
Obesity is an important and independent risk factor
for CVD and is strongly associated with dyslipidaemia,
insulin resistance and type 2 diabetes [29]. Research on
the effects of long-term flavonoid dietary supplementa-
tion in obese or normal body mass mice, in comparison
with diet without addition of these substances, showed
improved lipid profile, decreased insulin resistance and
reduced visceral adipose tissue mass. The non-obese
mice that consumed flavonoids demonstrated reduced
levels of atherogenic cholesterol fractions (non-HDL
cholesterol) [29]. These findings confirm the protective
effects of flavonoids on the cardiovascular system.
Effectiveness of flavonoids in prevention of age-
-related neurodegenerative diseases has been much
investigated in the recent years. It concerns particularly
dementia, Parkinson’s and Alzheimer’s diseases. It se-
ems that flavonoids can modulate neuronal function [21,
26, 34, 38]. Diets rich in these substances were shown
to beneficially affect maintenance of human cognitive
functions, probably through protection of neurons,
enhancement of their function and regeneration [38].
Reactive oxygen and nitrogen species are involved in
the development of many neurodegenerative diseases,
whilst dietary flavonoids have been shown to counteract
effectively oxidative neuronal damage.
It was demonstrated that use of the extract from
the gingobiloba plant, that is rich in flavonoids, may
beneficially influence treatment of the age-related
dementia and Alzheimer’s disease [1]. Tangeretin, a
flavonoid that belongs to the flavone subclass, found
mainly in citrus fruits, was shown to provide protection
in Parkinson’s disease. Animal models of this condition
is based on striatal damage by the neurotoxic substance
6-hydroxydopamine, what in turn leads to damage of the
nigrostriatal pathway that connects the substantia nigra
with the striatum. The latter is responsible, amongst
others, for planning of body movements. Damage of
this area underlies Parkinson’s disease. It was shown
that tangeretin given to mice passes the blood-brain
barrier (BBB) and protects the nigrostriatal pathway
against adverse effects of 6-hydroxydopamine [8].
The PAQUID study (Personnes Age’es QUID), pu-
blished in 2007, convincingly demonstrated that dietary
flavonoids in the elderly support their cognitive functions
[16]. The 10 years long observation was performed in
1640 subjects aged above 65 years, free from dementia
at baseline. The data about flavonoid consumption were
obtained by means of a food frequency questionnaire
that listed foodstuffs containing these substances. At
each visit (four times) every subject underwent cogni-
tive tests including Mini-Mental State Examination,
Benton’s Visual Retention Test and the ‘Isaacs’ Set
Test. Participants whose flavonoid intake was in the
two highest quartiles (ie. above 13.6 mg/day) had better
cognitive function after 10 years than those who consu-
med less of these compounds. Moreover, subjects who
ingested the least amounts of flavonoids (below 10.38
mg/day), lost on average 2.1 points in the Mini-Mental
State Examination scale, while those with the highest
consumption (above 17.7 mg/day) lost only 1.2 points.
These findings demonstrated that regular consumption
of dietary flavonoids exerts beneficial effect on cognitive
function maintenance during aging [16].
The multitude of effects resulting from consum-
ing flavonoids, both with foodstuffs and concentrated
sources, appears to be related to two parallel processes.
The first is regulation of the neuronal signal cascade
what results in the inhibition of cell apoptosis that is
caused by the action of neurotoxic substances. This
promotes neuronal survival and differentiation [34].
Secondly, flavonoids seem to exert beneficial effects on
the peripheral and central nervous systems by generation
of changes in the cerebral blood flow. This can induce
angiogenesis and growth of new nerve cells in the hip-
pocampus. These processes are important for mainte-
nance of neuronal and cognitive brain functions [34].
It seems that regular consumption of foods rich in
flavonoids reduces the risk of neurodegenerative dis-
eases and counteracts or delays the onset of age-related
cognitive disorders. However, mechanisms of flavonoid
action are not entirely clear. The question then arises as
to when to use these substances to ensure their optimal
effectiveness and which of them produce the strongest
protection of the nervous system. Further studies on
this wide group of compounds are therefore necessary
to provide satisfactory answers to these questions.
Chemoprevention is defined as the use of natural or
synthetic substances to inhibit or reverse carcinogene-
sis [24]. Much attention, in this respect, is focused on
flavonoids [4, 5, 10, 14, 19, 28, 35]. Epidemiological
and clinical studies suggest that these compounds can
prevent cancer through their interaction with various
genes and enzymes [4]. It seems that biologically active
substances found in foodstuffs may affect such stages of
carcinogenesis as initiation, promotion and progression
[24]. Many mechanisms of flavonoid action have been
discovered. In the initiation and promotion stages, they
include: inactivation of the carcinogen, inhibition of cell
proliferation, enhancement of DNA repair processes,
and reduction of oxidative stress. In the progression
phase flavonoids may induce apoptosis, inhibit angio-
Flavonoids – food sources and health benefits 83Nr 2
genesis, exhibit antioxidant activity, and also cytotoxic
or cytostatic action against cancer cells [4, 19, 24, 40].
Prevention of metabolic activation of procarcino-
gens is related to flavonoid interaction with phase I
enzymes that are responsible for metabolism of various
endogenous or exogenous substrates. This results from
inhibition of the cytochrome P450 enzymes, such as
CYP1A1 and CYP1A2. Flavonoids thus protect against
cellular damage arising from the activation of carcinoge-
nic factors. Another mechanism of their action is related
to reinforcement of mutagen detoxification through
induction of the phase II enzymes, such as glutathione
S-transferase (GST) and UDP-glucuronyl transferase
(UDP-GT), which detoxify and eliminate carcinogens
from the body [4, 15].
The anticancer effects of flavonoids can also be
explained by the cell cycle inhibition. There are two
classes of regulatory molecules responsible for cell
cycle progression: cyclins and cyclin-dependent kina-
ses (CDKs), which are activated under the influence
of mitogenic signals within the cell. The uncontrolled
activation of CDKs plays a key role in the pathoge-
nesis of cancer. Various types of cancer are linked to
excessive CDKs activity through gene mutation. For
this reason, much research is increasingly focused on
substances that can inhibit or modulate CDKs. These
actions may exhibited by such flavonoids as: genistein,
quercetin, daidzein, luteolin, kaempferol, apigenin, and
Current evidence about the anticarcinogenic po-
tential of flavonoids are however still equivocal. Some
studies, that were performed in animals or various cell
models, indicate that certain flavonoids may inhibit both
cancer initiation and progression [10, 30, 37]. However,
experiments on rats, conducted to determine the effect of
tangeretin and quercetin on the risk of cancer occurrence
arising from alphatoxin B1 induction (initiation and
promotion of hepatic cancer) showed that whereas tan-
geretin administrated during tumour initiation reduced
the number of precancerous lesions, quercetin did not
exhibit such effect [30]. Another study showed that the
development of lung cancer in mice exposed to tobacco
smoke was arrested by consumption of both black and
green teas. The results demonstrated that catechins con-
tained in tea may protect against development of cancer
[37]. A further research that tested influence of selected
compounds on cultured human liver cells demonstrated
that luteolin and apigenin also provided effective pro-
tection against cancer development. These flavonoids
seem to inhibit CDKs. However, other studies indicate
that flavonoids have weaker actions in vivo compared
to that in vitro [11, 32]. An investigation on whether
quercetin prevents lung cancer in mice showed that this
substance, in spite of its strong biological activity, is
not absorbed by these animals efficiently enough. The
authors however suggest that further work should be
focused on making the absorption mechanism of this
substance more effective what would probably promote
the expected anticancer action [32].
The studies quoted above were performed in ani-
mals, and so the conclusions should be extrapolated to
humans with caution. Observational studies conducted
on various human populations are also equivocal [10,
14, 35]. The Iowa Women’s Health Study investigated
the effect of dietary flavonoid consumption on the inci-
dence of cancer of the lung, colon, breast and pancreas
in 34,708 post-menopausal women who were observed
in 1986 – 2004. Their dietary habits were determined by
means of a food frequency questionnaire. Results sho-
wed that regular flavonoid consumption significantly
reduced the risk of the lung cancer, particularly in the
women who had stopped smoking. However, there was
no evident effect of flavonoid consumption on the risk
of other cancers [5]. Another study, performed in 34,408
women (aged above 45 years), demonstrated no signi-
ficant link between intake of foods rich in flavonoids
and the risk of cancer [35]. Despite of these findings,
a meta-analysis of 12 studies showed a reduced risk of
breast cancer in women, especially postmenopausal,
who consumed large amounts of flavonoids, such as fla-
vonols and flavones [14]. Further studies are therefore
required to assess the promising influence of flavonoids
on the human body.
Flavonoids exhibit manifold effects in protection of
the human body. However, the underlying mechanisms
are still not fully understood. According to current
knowledge, a diet that includes flavonoid containing
products should be promoted. Among foods that pro-
vide large amounts of these substances there are: citrus
fruits, blueberries, blackberries, onions, peppers, a
variety of teas, and also oregano and parsley. However,
it should be emphesized that toxicity of flavonoids con-
sumed in large doses remains unknown. For this reason,
use of their dietary supplements should be considered
with caution. The question arises as to when to use these
substances to enable their most effective action, and as
to which flavonoids are the most beneficial to human
health. It is presumed that flavonoids exert stronger
effects in vitro than in vivo, and thus it is important to
determine their mechanisms of action at the molecular
level. Further studies in this area are therefore greatly
This paper was financed by the Warsaw Medical Uni-
versity, Poland
A. Kozłowska, D. Szostak-Węgierek
84 Nr 2
Conflict of interest
The authors declare no conflict of interest.
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Received: 07.11.2013
Accepted: 12.03.2014
... Anthocyanin, another flavonoid, has been shown to improve blood lipids by reducing serum TG, LDL-c levels and apolipoprotein B (apo-B), while increasing HDL-c and apolipoprotein A (apo-A) levels (35,36) . Experimental and cellular studies have proposed several mechanisms to explain these effects; including anthocyanins ability (1) to down-regulate hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, (2) to inhibit cholesteryl ester transporter (CETP), (3) to reduce the production/release of apo-B and apolipoprotein CIII (apo-CIII) and finally (4) to enhance the expression of LDL-c receptors (35,37) . ...
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Plums are abundant in bioactive compounds which have been associated with numerous health benefits. In the present study, we aimed at examining the impact of plum supplementation on lipid profile of individuals. Electronic bibliographical databases were searched for relevant randomised clinical trials. Articles meeting our eligibility criteria were included for data extraction and final analysis. Weighted mean difference (WMD) was estimated using a random-effect model. Of the total articles retrieved in the initial search, nine articles were found to be eligible to be included in the analysis. Our results show that plum supplementation significantly improves total cholesterols levels in the unhealthy individuals. Moreover, plum supplementation reduces the LDL-c levels in the pooled sample (WMD = −11⋅52 mg/dl; 95 % CI −21⋅93, −1⋅11, P = 0⋅03, I ² = 98⋅7 %) and also in some of the subgroups of individuals (dried plum, unhealthy subjects, duration more than 8 weeks). Moreover, it had a significant reducing effect on TC levels just in unhealthy subjects. Although plum supplementation did not have any significant impact on serum levels of TG nor HDL-c. Our results show that supplementation with plums is potentially effective in reducing serum total cholesterol and LDL-c.
... Fourth, nuts and legumes that provide a good source of polyphenols, including flavonoids and proanthocyanidins, are also recommended in the DASH diet. The growing body of scientific evidence indicates that flavonoids can prevent cancer through inactivation of carcinogens, inhibition of cell proliferation, enhancement of DNA repair processes, and reduction in oxidative stress (54). Besides, a previous study by Fillon (55) has also shown that these components might decrease the risk of cancer. ...
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Background Despite increasing evidence for the association of adherence to the Dietary approaches to stop hypertension (DASH) diet with breast cancer risk, the results remain inconclusive. The purpose of the current systematic review was to summarize the evidence from previous observational studies and explore the potential association between DASH diet and breast cancer risk using meta-analysis. Methods A comprehensive literature search was conducted using the databases of PubMed, Web of Science, CNKI and Wanfang Data to identify the relevant publications from inception up to July 2022. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest categories of DASH score in relation to breast cancer risk, using a random-effects model. The Cochran’s Q test and I-squared ( I ² ) statistic were used to detect the sources of heterogeneity among the included studies. Results Overall, eleven studies, involving 23,254 breast cancer cases and 449,273 participants, were included in this systematic review and meta-analysis. Combining 16 effect sizes from 11 studies, a significant inverse association between adherence to the DASH diet and risk of breast cancer was observed (RR = 0.79; 95% CI: 0.70, 0.90, P < 0.0001). Stratified analysis showed a significant association between adherence to the DASH diet and risk of breast cancer in case-control studies (RR = 0.49; 95% CI: 0.27–0.89, P = 0.019), and a marginally significant association in prospective cohort studies (RR = 0.92; 95% CI: 0.86–0.98, P = 0.014), respectively. Besides, a more significant association between DASH score and reduced risk of breast cancer was observed in Asian countries (RR = 0.50; 95% CI: 0.31–0.81, P = 0.005) than in the United States (RR = 0.93; 95% CI: 0.89–0.99, P = 0.012). Similarly, when we conducted analyses separately by menopausal status, we found a significant inverse association between DASH diet and breast cancer risk in postmenopausal women (RR = 0.58; 95% CI: 0.39–0.87, P = 0.008). Conclusion The results of this systematic review and meta-analysis indicate a significant inverse association between adherence to the DASH diet and risk of breast cancer. Further large prospective studies and randomized controlled trials are required to confirm our findings.
... Thus, flavonoids are a regular part of human diet [10,13]. For a more detailed review about flavonoid food sources, please see Kozłowska and Szostak-Węgierek, 2017 [81]. Flavonoids can be divided into classes and share a basic chemical structure. ...
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Asthma is a chronic disease with increasing prevalence and incidence, manifested by allergic inflammatory reactions, and is life-threatening for patients with severe disease. Repetitive challenges with the allergens and limitation of treatment efficacy greatly dampens successful management of asthma. The adverse events related to several drugs currently used, such as corticosteroids and β-agonists, and the low rigorous adherence to preconized protocols likely compromises a more assertive therapy. Flavonoids represent a class of natural compounds with extraordinary antioxidant and anti-inflammatory properties, with their potential benefits already demonstrated for several diseases, including asthma. Advanced technology has been used in the pharmaceutical field to improve the efficacy and safety of drugs. Notably, there is also an increasing interest for the application of these techniques using natural products as active molecules. Flavones, flavonols, flavanones, and chalcones are examples of flavonoid compounds that were tested in controlled delivery systems for asthma treatment, and which achieved better treatment results in comparison to their free forms. This review aims to provide a comprehensive understanding of the development of novel controlled delivery systems to enhance the therapeutic potential of flavonoids as active molecules for asthma treatment.
... They represent a large family of compounds consisting of benzopyran rings with polyphenolic groups at different positions. The structure of flavonoids consists of 15 carbons and two rings (A and B) linked by three carbon chains [20] (Figure 1). Flavonoids are classified into multiple types based on their chemical structure, unsaturated linking chain, and degree of oxidation [21]. ...
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Simple Summary: The consumption of flavonoids positively influences the same (impaired) metabolic pathways in diabetes and gastrointestinal cancers, leading to the hypothesis that flavonoids could exert dual effects on these diseases, as some flavonoids can target the same pathways in both conditions, such as the apoptosis and AMPK pathways. Here, we identified flavonoids with such interactions and discussed their positive effects on both diseases. Nevertheless, more efforts are required to estimate the appropriate flavonoid dosage and flavonoid-flavonoid interactions, and to identify potential side effects. It is also necessary to assess the possibility of combining multiple flavonoids with the currently used treatment. Abstract: Diabetes and gastrointestinal cancers (GI) are global health conditions with a massive burden on patients' lives worldwide. The development of both conditions is influenced by several factors, such as diet, genetics, environment, and infection, which shows a potential link between them. Flavonoids are naturally occurring phenolic compounds present in fruits and vegetables. Once ingested, unabsorbed flavonoids reaching the colon undergo enzymatic modification by the gut microbiome to facilitate absorption and produce ring fission products. The metabolized flavonoids exert antidiabetic and anti-GI cancer properties, targeting major impaired pathways such as apoptosis and cellular proliferation in both conditions, suggesting the potentially dual effects of flavonoids on diabetes and GI cancers. This review summarizes the current knowledge on the impact of flavonoids on diabetes and GI cancers in four significant pathways. It also addresses the synergistic effects of selected flavonoids on both conditions. While this is an intriguing approach, more studies are required to better understand the mechanism of how flavonoids can influence the same impaired pathways with different outcomes depending on the disease.
... The level of polyphenols contained in vegetables and fruit, for example, depends on the type of cultivation, crop variety and location, as well as the specific morphology of the plant source. In addition, ethnic differences in food structure or cultural differences in the storage and preparation of foods, particularly those of vegetables might also account for this result [34,35]. Other factors which might explain the geographic disparities found, beyond polyphenols, include the fact that the populations surveyed differ for other characteristics, as do the studies reviewed. ...
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Background: Phenolic compound consumption may have a protective effect against gastric cancer (GC). Most GC studies focus on the flavonoids class, but results are conflicting and knowledge gaps remain for other classes and total polyphenol intake. This study aimed to assess the association between polyphenol intake (total, flavonoids, and other classes) and GC. Methods: In this systematic review and meta-analysis, the PubMed, Embase, Scopus, LILACS, Web of Science, and OpenGrey databases were searched for studies published up to 20 March 2022. Case-control and cohort studies analyzing the association between polyphenol intake and GC were included. For the meta-analysis, pooled summary estimates were calculated using a random-effects model, and the estimates extracted adjusted for most variables. Subgroup analyses were performed for subclass (e.g., flavonoids and other classes), sex, geographical area, study design, anatomical subtype, histological subtype, family history of GC and fruit and/or vegetable intake. The study was registered with PROSPERO (#CRD42022306014). Findings: The search identified 2752 records, of which 19 studies published during the period 1999-2021 including a total of 1,197,857 subjects were eligible. Polyphenol consumption reduced GC risk by 29% (RR = 0.71; 95% CI: 0.62-0.81; I2 = 60.5%); while flavonoid intake decreased GC risk by 28% (RR = 0.72; 95% CI: 0.61-0.85; I2 = 64.3%), similar to the reduction fort other classes (RR = 0.65; 95% CI: 0.54-0.79; I2 = 72.0%). Protective effects against GC were observed in both sexes (male, RR = 0.79; 95% CI: 0.67-0.94, I2 = 31.6%; female, RR = 0.65; 95% CI: 0.48-0.87, I2 = 49.7%) and for intestinal subtype (RR = 0.65; 95% CI: 0.52-0.82, I2 = 0.0%). By continent, polyphenol consumption reduced GC risk in both Europe (RR = 0.67; 95% CI: 0.57-0.79, I2 = 44.2%) and Asia (RR = 0.67; 95% CI: 0.51-0.89, I2 = 60.7%). Conclusions: Dietary polyphenol intake decreased GC risk. The reduction was greatest in females. Most previous studies were carried out in Europe and Asia. Further studies investigating polyphenol consumption and GC in Latin American populations are warranted.
... Flavonoids are another class of metabolites identified in the curcuma sample. These bioactive phytoconstituents have remarkable pharmacological proprieties, including antioxidant, antitumoral, antimicrobial and anti-inflammatory activities, as well as effects against neurodegenerative diseases (Alzheimer's disease) [74,96,101,[108][109][110][111]. ...
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Curcuma is one of the most famous medicinal and tropical aromatic plants. Its health benefits have been appreciated and exploited in traditional Asian medicine since ancient times. Various studies have investigated its complex chemical composition and demonstrated the remarkable therapeutic properties of curcuma’s phytoconstituents. Oxidative stress is a decisive driving factor triggering numerous pathologies (neurodegenerative, psychiatric and cardiovascular diseases; diabetes; tumors, etc.). Numerous recent studies have focused on the use of natural compounds and nanomaterials as innovative molecular targeting agents as effective therapeutic strategies. In this study, we report, for the first time, the development of a simple target phytocarrier system that capitalizes on the bioactive properties of curcuma and AgNPs. The complete metabolic profile of curcuma was determined based on gas chromatography-mass spectrometry (GC-MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS). A total of 80 metabolites were identified under mass spectra (MS)-positive mode from 10 secondary metabolite categories: terpenoids, amino acids, diarylheptanoids, flavonoids, phenolic acids, steroids, fatty acids, coumarins, alkaloids and miscellaneous. In addition, the biological activity of each class of metabolites was discussed. A comprehensive characterization (FT-IR, UV-Vis, DLS, SEM, TEM, EDS, zeta potential and XRD) was performed to study the morphostructural properties of this new phytocarrier system. Antioxidant activity of the new phytocarrier system was evaluated using a combination of in vitro methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and cyclic voltammetric method (Trolox equivalent antioxidant capacity (TEAC) electrochemical assay)). Antioxidants assays showed that the phytocarrier system exhibits superior antioxidant properties to those of its components, i.e., curcuma or citrate-coated-AgNPs. These data confirm the potential to enhance relevant theoretical knowledge in the area of innovative antioxidant agents, with potential application in neurodegenerative therapeutic strategies.
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Background: Anthocyanin-rich red cabbage is known to reduce hepatic enzymes levels such as SGPT, SGOT, ALP, and GGT in drug-induced liver injury (DILI). Objective: This study aimed to determine the effect of red cabbage juice on SGOT, ALP, and GGT levels in acetaminophen-induced liver injury in rats.Methods: This was an experimental study using a post-test-only control group design. Thirty male Wistar rats were randomly divided into 5 groups. K1 was the negative control. K2, K3, K4, and K5 were pretreated with 300 mg acetaminophen. K3, K4, and K5 were treated with 0.5 g/ml of red cabbage juice, 0.7 g/ml of red cabbage juice, and 0.9 g/ml of red cabbage juice respectively. Data were analyzed using one-way ANOVA and post hoc LSD (p<0.05). Results: There was no significant difference in SGOT and GGT levels among the groups p=0.271(p>0.05) and p=0.053 (p>0.05) respectively. Whereas ALP levels showed significant differences among the groups p=0.000 (p<0,05) respectively. Conclusion: The administration of red cabbage in any dose had no effect on SGOT and GGT levels in acetaminophen-induced liver injury in rats whereas in ALP, the most effective dose to cause an effect is 0.5 g/ml.
In Mexico, plants are commonly used to alleviate various ailments, including controlling some chronic degenerative diseases through the regular consumption of decoctions, infusions, and teas. However, there is little scientific evidence consolidating traditional medicine within health systems. Therefore, this work determined the phytochemical profile of the most used plants to treat various ailments (Cedro rojo, Cancerina, Ortiguilla, Hierba de la golondrina, Hierba de arlomo) and their general consumption as infusions. Aqueous and ethanolic extracts were generated, while the phytochemical compound content in the extracts obtained was quantified. The results indicate that the ethanolic extracts showed the highest phenolic compound and tannin content, with the highest contents for Cedro rojo (831.04 mg∙L‐1) and Cancerina (864.80 mg∙L‐1). The antioxidant activity was also determined, and a significant difference was observed (p < 0.05). The extracts with the highest antioxidant capacity were the ethanolic extracts ranging from 250 to 907 µMET∙mL‐1, while the aqueous extracts ranged from 112 to 390 µMET∙mL‐1. The compounds identified by high‐performance liquid chromatography characterization on the aqueous extracts highlighted the presence of chlorogenic acid > cinnamic acid > quercetin. In ethanolic extracts, the presence of chlorogenic acid > cinnamic acid > quercetin > gallic acid > ferulic acid > coumaric acid was highlighted. The correlation between bioactive compounds, type of extract, and antioxidant activity suggests a significant affinity of these phytochemical compounds for the ethanol solvent. The results indicate that these plants are good sources of antioxidant phenolics and can be incorporated for use as functional beverages. However, more studies are needed to corroborate their beneficial effect.
Low temperature is among the most restrictive factors to limit the yield and distribution of pear. Pyrus hopeiensis is a valuable wild resource. PCA showed that P. hopeiensis had strong cold resistance. In this study, the mRNA and metabolome sequencing of P. hopeiensis flower organs exposed to different low temperatures were performed to identify changes of genes and metabolites in response to low-temperature stress. A total of 4 851 differentially expressed genes (DEGs) were identified. Trend analysis showed that these DEGs were significantly enriched in profiles 19, 18, 7, 14, 1, 4 and 11. And the KEGG enrichment analysis showed that the DEGs in profile 18 were significantly enriched in flavone and flavonol biosynthesis. Besides, the expressed trends as well as GO and KEGG functional enrichment analyses of DEGs under cold and freezing stress showed significantly difference. Analyses of flavonoid-related pathways indicated that flavonoid structural genes had undergone significant changes. Correlation analysis showed that bHLH and MYB TFs may affect flavonoid biosynthesis by regulating structural gene expression. And PhMYB308 and PhMYB330 were likely candidate repressors of flavonoid biosynthesis by binding to a specific site in bHLH proteins. In total, 92 differentially accumulated metabolites (DAMs) were identified in P. hopeiensis flowers including 12 flavonoids. WGCNA results showed that coral1, pink and brown4 modules were closely associated with flavonoids and 11 MYBs and 15 bHLHs among the three modules may activate or inhibit the expression of 23 structural genes of flavonoid biosynthesis. Taken together, the results of this study provided a theoretical basis for further exploration of the molecular mechanisms of flavonoid biosynthesis and cold resistance of P. hopeiensis flower organs and our findings laid a foundation for further molecular breeding in cold-resistant pear varieties.
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The spike glycoprotein (S protein), 3-chymotrypsin-like protease (3CL-Pro), and papain-like protease (PL-Pro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus are widely targeted for the discovery of therapeutic compounds against this virus. Dietary flavonoid compounds were proposed as a candidate for safe therapy for COVID-19 patients. Nevertheless, wet lab experiments for high-throughput screening of the compounds are undoubtedly time and cost consuming. This study aims to screen dietary flavonoid compounds that bind to S protein, 3CL-Pro, and PL-Pro of SARS-CoV-2. For this purpose, protein structures of the receptor-binding domain (RBD) of S protein (6M0J), 3CL-Pro (6LU7), and PL-Pro (6W9C) were retrieved from the RCSB Protein Data Bank (PDB). Twelve dietary flavonoid compounds were selected for the studies on their binding affinity to the targeted proteins by global and local docking. The docking and molecular dynamic (MD) simulations were performed using YASARA software. Out of 12 compounds, the highest binding score was observed between hesperidin against RBD S protein (−9.98 kcal/mol), 3CL-Pro (−9.43 kcal/mol), and PL-Pro (−8.89 kcal/mol) in global docking. Interestingly, MD simulation revealed that the complex between 3CL-Pro and RBD S protein has better stability than PL-Pro. This study suggests that hesperidin might have versatile inhibitory properties against several essential proteins of SARS-CoV-2. This study, nevertheless, remains to be confirmed through in vitro and in vivo assays.
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Phenolic compounds are a group of key plant metabolites found abundantly in fruit and vegetables. Because of their antioxidant properties, they play a significant role in preventing various degenerative illnesses, tumours or cardiovascular disease. In nature, they are present in foods mainly as esters, glycosides and polymers which need to undergo enzymatic hydrolysis in the digestive tract or by the gut microflora before becoming absorbed. The biological properties of these phenolic compounds undergoing this degradation, are thus governed by their absorption as well as metabolism. Many methods are used to assess the rates and the degrees to which these substances are digested and absorbed, both in vivo and in vitro ones, where the former are the most reliable, although they suffer from various limitations. For this reason, many in vitro models have now arisen to simulate the function of human digestion in the attempt to faithfully re-create real-life conditions. Mechanisms of polyphenols absorption have been principally studied by intestinal epithelial cell models, in particular, those using the Caco-2 cell line.
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Studies have suggested the chemopreventive effects of flavonoids on carcinogenesis. Yet numbers of epidemiologic studies assessing dietary flavonoids and breast cancer risk have yielded inconsistent results. The association between flavonoids, flavonoid subclasses (flavonols, flavan-3-ols, etc.) and the risk of breast cancer lacks systematic analysis. We aimed to examine the association between flavonoids, each flavonoid subclass (except isoflavones) and the risk of breast cancer by conducting a meta-analysis. We searched for all relevant studies with a prospective cohort or case-control study design published before July 1(st), 2012, using Cochrane library, MEDLINE, EMBASE and PUBMED. Summary relative risks (RR) were calculated using fixed- or random-effects models. All analyses were performed using STATA version 10.0. Twelve studies were included, involving 9 513 cases and 181 906 controls, six of which were prospective cohort studies, and six were case-control studies. We calculated the summary RRs of breast cancer risk for the highest vs lowest categories of each flavonoid subclass respectively. The risk of breast cancer significantly decreased in women with high intake of flavonols (RR = 0.88, 95% CI 0.80-0.98) and flavones (RR = 0.83, 95% CI: 0.76-0.91) compared with that in those with low intake of flavonols and flavones. However, no significant association of flavan-3-ols (RR = 0.93, 95% CI: 0.84-1.02), flavanones (summary RR = 0.95, 95% CI: 0.88-1.03), anthocyanins (summary RR = 0.97, 95% CI: 0.87-1.08) or total flavonoids (summary RR = 0.98, 95% CI: 0.86-1.12) intake with breast cancer risk was observed. Furthermore, summary RRs of 3 case-control studies stratified by menopausal status suggested flavonols, flavones or flavan-3-ols intake is associated with a significant reduced risk of breast cancer in post-menopausal while not in pre-menopausal women. The present study suggests the intake of flavonols and flavones, but not other flavonoid subclasses or total flavonoids, is associated with a decreased risk of breast cancer, especially among post-menopausal women.
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Purpose: Polyphenols play an important role in the prevention of degenerative diseases, particularly cardiovascular diseases and cancers. The purpose was to estimate dietary polyphenol intake in Polish adults, using own database of food polyphenols, and to establish main dietary sources of polyphenols. Material and methods: Polish men and women (6661) aged 20-74 years were randomly selected from the Polish National Multicenter Health Survey (WOBASZ). Subjects` daily food consumption was estimated by the 24-hour recall method and was continued for 3 years. It was determined on this basis, that 96 plant foods and plant food products were consumed. The own dietary database of polyphenol contents in food was used to calculate polyphenol intakes in the subjects. The daily total polyphenol intakes were calculated for both genders in individual age categories: 20-40 years, 41-60 years and 61-74 years. Results: The average polyphenol consumption for the men was 1172 mg/day, and for the women it made 1031 mg/day. Plant food categories such as beverages, vegetables, fruits and cereals were found to be significant sources of polyphenols, of which tea, coffee, potatoes, apples and white bread were the main contributors. Conclusions: The amount of polyphenol consumption in Polish adult population is similar to the polyphenol intake in other countries populations, accounting roughly for 1g of polyphenols for both genders and different age groups. Patterns of polyphenol consumption, however, vary for genders and age groups. Polyphenols are characterized by a spectrum of antioxidant capabilities, therefore future studies should focus on dietary intakes of individual polyphenols.
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Flavonoids are polyphenolic compounds with potential antioxidant activity via multiple reduction capacities. Oxidation of cellular lipids has been implicated in many diseases. Consequently, this study has assessed the ability of several dietary flavonoid aglycones to suppress lipid peroxidation of hepatic microsomes derived from rats deficient in the major lipid soluble antioxidant, dα-tocopherol. Antioxidant effectiveness was galangin > quercetin > kaempferol > fisetin > myricetin > morin > catechin > apigenin. However, none of the flavonoids were as effective as dα-tocopherol, particularly at the lowest concentrations used. In addition, there appears to be an important distinction between the in vitro antioxidant effectiveness of flavonoids and their ability to suppress indices of oxidation in vivo. Compared with dα-tocopherol, repletion of vitamin E deficient rats with quercetin, kaempferol, or myricetin did not significantly affect indices of lipid peroxidation and tissue damage. Direct antioxidant effect of flavonoids in vivo was not apparent probably due to low bioavailability although indirect redox effects through stimulation of the antioxidant response element cannot be excluded.
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Realizing the therapeutic benefits of quercetin is mostly hampered by its low water solubility and poor absorption. In light of the advantages of nanovehicles in the delivery of flavanoids, we aimed to deliver quercetin perorally with nanomicelles made from the diblock copolymer, polyethylene glycol (PEG)-derivatized phosphatidylethanolamine (PE). Quercetin-loaded nanomicelles were prepared by using the film casting method, and were evaluated in terms of drug incorporation efficiency, micelle size, interaction with Caco-2 cells, and anticancer activity in the A549 lung cancer cell line and murine xenograft model. The incorporation efficiency into the nanomicelles was ≥88.9% when the content of quercetin was up to 4% w/w, with sizes of 15.4-18.5 nm and polydispersity indices of <0.250. Solubilization of quercetin by the nanomicelles increased its aqueous concentration by 110-fold. The quercetin nanomicelles were stable when tested in simulated gastric (pH 1.2) and intestinal (pH 7.4) fluids, and were non-toxic to the Caco-2 cells as reflected by reversible reduction in transepithelial electrical resistance and ≤25% lactose dehydrogenase release. The anticancer activity of quercetin could be significantly improved over the free drug through the nanomicellar formulation when tested using the A549 cancer cell line and murine xenograft model. The nanomicellar quercetin formulation was well tolerated by the tumor-bearing animals, with no significant weight loss observed at the end of the 10-week study period. A stable PEG-PE nanomicellar formulation of quercetin was developed with enhanced peroral anticancer activity and no apparent toxicity to the intestinal epithelium.
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Flavonoids are plant-based phytochemicals with cardiovascular protective properties. Few studies have comprehensively examined flavonoid classes in relation to cardiovascular disease mortality. We examined the association between flavonoid intake and cardiovascular disease (CVD) mortality among participants in a large, prospective US cohort. In 1999, a total of 38,180 men and 60,289 women in the Cancer Prevention Study II Nutrition Cohort with a mean age of 70 and 69 y, respectively, completed questionnaires on medical history and lifestyle behaviors, including a 152-item food-frequency questionnaire. Cox proportional hazards modeling was used to calculate multivariate-adjusted hazard RRs and 95% CIs for associations between total flavonoids, 7 flavonoid classes, and CVD mortality. During 7 y of follow-up, 1589 CVD deaths in men and 1182 CVD deaths in women occurred. Men and women with total flavonoid intakes in the top (compared with the bottom) quintile had a lower risk of fatal CVD (RR: 0.82; 95% CI: 0.73, 0.92; P-trend = 0.01). Five flavonoid classes-anthocyanidins, flavan-3-ols, flavones, flavonols, and proanthocyanidins-were individually associated with lower risk of fatal CVD (all P-trend < 0.05). In men, total flavonoid intakes were more strongly associated with stroke mortality (RR: 0.63; 95% CI: 0.44, 0.89; P-trend = 0.04) than with ischemic heart disease (RR: 0.90; 95% CI: 0.72, 1.13). Many associations appeared to be nonlinear, with lower risk at intakes above the referent category. Flavonoid consumption was associated with lower risk of death from CVD. Most inverse associations appeared with intermediate intakes, suggesting that even relatively small amounts of flavonoid-rich foods may be beneficial.
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There is increasing interest in the potential health benefits of dietary flavonoids. Fruits and vegetables, tea, and cocoa are rich natural sources of flavonoids. Epidemiological studies have indicated that consumption of these foods is likely to be associated with a reduced risk of cardiovascular disease, but the etiology of this benefit is not yet clearly defined. Furthermore, in some acute interventions, a positive effect of tea and cocoa on vascular function has been reported. An alternative source of flavonoids is dietary supplements, which have become increasingly popular in the recent past. In this context, it needs to be critically evaluated whether vascular health-promoting and other positive properties of flavonoid-rich diets can be replaced by purified flavonoids as dietary supplements. Plant sources of flavonoids contain a complex mixture of secondary plant metabolites and not only flavonoids per se. This complex mixture of secondary plant metabolites cannot be simply exchanged by single purified compounds as dietary supplements. If flavonoids are given as dietary supplements, toxicity issues as well as nutrient drug interactions need to be taken into account. Purified flavonoids given in high doses as dietary supplements may affect trace element, folate, and vitamin C status. Furthermore, they may exhibit antithyroid and goitrogenic activities. In this review article, the available literature on the safety issues surrounding high dose supplemental flavonoid consumption has been summarized.
Flavonoids are plant components of the diet. Their daily intake is about 1 g. In Poland the main source of flavonoids is tea, apples and onions. These compounds are characterized by a variety of biological activities and pharmacological effects. Especially important for human health are their antioxidant properties. This paper presents the current state of knowledge on the role and importance of flavonoids in the prevention of the initiation and development of cardiovascular diseases. Epidemiological observations, clinical research, in vitro and in vivo experimental studies clearly show a protective effect of flavonoids on the cardiovascular system. Their beneficial effects on the cardiovascular system involve the inhibition of low density lipoprotein (LDL) oxidation, the reduction of blood vessels permeability, antiplatelet and anti-inflammatory activity, and hypotensive and direct vasodilator action. Biological potential of flavonoids (especially the antioxidant activity) indicates the possibility of their use in primary and secondary prevention of atherosclerosis and its clinical consequences (heart attack, stroke, and others) as a safe potential therapeutic agents.
DNA-damaging drugs constitute standard chemotherapy regimen for advanced colorectal cancer. Here, the interactions between quercetin and 5-fluorouracil (5-FU), etoposide, and camptothecin were examined in cancer cells. HCT116 colorectal or PPC1 prostate cancer cells were treated with quercetin and the drugs. Clonogenicity assays, cell cycle profiles, and expressions of p53, p21, BAX, survivin and cyclin B1 proteins were used to examine the effects of the treatments. Quercetin synergistically inhibited the clonogenicity of the wild-type cells, but inhibited the cell cycle effects of all the drugs tested. In p53-null cells, the combination of low dose 5-FU with up to 6 μM quercetin promoted clonogenic survival. Treatment of p53-wild-type cells with 50 μM quercetin reduced drug-induced up-regulation of p53, p21 and BAX. The combination of quercetin and the drugs also reduced the levels of cyclin B1 and survivin proteins. While high doses of quercetin synergize with DNA-damaging agents, the effect of drug combination with quercetin is influenced by the effective doses and the p53 status of the cells.